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Myelodysplasias

Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation

Leukemia volume 25, pages 449–454 (2011)Cite this article

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Abstract

We describe 70 children with myelodysplastic syndrome (MDS) (refractory cytopenia (n=31) and refractory anemia with excess blasts (n=30) or blasts in transformation (n=9)) who received umbilical cord blood (UCB) transplantation with a single UCB unit and a myeloablative conditioning regimen. Approximately 20% of children had secondary MDS. Median age at transplantation was 7 years and the median follow-up was 3 years. The day-60 probability of neutrophil recovery was 76%; recovery was faster after transplantation of matched or 1-locus mismatched UCB, irradiation-containing conditioning regimen, cell dose >6 × 107/kg and monosomy 7. Risks of treatment failure (recurrent disease or death) were lower in patients with monosomy 7 and transplantations after 2001. The 3-year disease-free survival (DFS) was 50% for transplantations after 2001 compared with 27% for the earlier period (P=0.018). Transplantations after 2001 occurred within 6 months after diagnosis and used UCB units with higher cell dose. DFS was highest in patients with monosomy 7 (61%) compared with other karyotypes (30%), P=0.017. These data suggest that transplantation of mismatched UCB graft is an acceptable alternative for children without a matched sibling or suitably matched unrelated adult donor.

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References

  1. Locatelli F, Zecca M, Pession A, Maserati E, De Stefano P, Severi F . Myelodysplastic syndromes: the pediatric point of view. Haematologica 1995; 80: 268–279.

    CAS  PubMed  Google Scholar 

  2. Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR et al. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood 2003; 102: 1997–2003.

    Article  CAS  PubMed  Google Scholar 

  3. Hasle H, Baumann I, Bergstrasser E, Fenu S, Fischer A, Kardos G et al. The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML). Leukemia 2004; 18: 2008–2014.

    Article  CAS  PubMed  Google Scholar 

  4. Creutzig U, Bender-Gotze C, Ritter J, Zimmermann M, Stollmann-Gibbels B, Korholz D et al. The role of intensive AML-specific therapy in treatment of children with RAEB and RAEB-t. Leukemia 1998; 12: 652–659.

    Article  CAS  PubMed  Google Scholar 

  5. Guinan EC, Tarbell NJ, Tantravahi R, Weinstein HJ . Bone marrow transplantation for children with myelodysplastic syndromes. Blood 1989; 73: 619–622.

    CAS  PubMed  Google Scholar 

  6. Hasle H, Kerndrup G, Yssing M, Clausen N, Ostergaard E, Jacobsen N et al. Intensive chemotherapy in childhood myelodysplastic syndrome. A comparison with results in acute myeloid leukemia. Leukemia 1996; 10: 1269–1273.

    CAS  PubMed  Google Scholar 

  7. Locatelli F, Pession A, Bonetti F, Maserati E, Prete L, Pedrazzoli P et al. Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes. Leukemia 1994; 8: 844–849.

    CAS  PubMed  Google Scholar 

  8. Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.

    Article  CAS  PubMed  Google Scholar 

  9. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.

    Article  PubMed  Google Scholar 

  10. Picardi A, Del Principe D, Cudillo L, Dentamaro T, Amadori S, de Fabritiis P . Unrelated cord blood transplantation for children with high risk myelodysplastic syndromes. Haematologica 2004; 89: ELT08.

    PubMed  Google Scholar 

  11. Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 2003; 17: 277–282.

    Article  CAS  PubMed  Google Scholar 

  12. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  13. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  14. Fine JP, Gray R . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

    Article  Google Scholar 

  15. Kaplan E . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  16. Cox DR . Regression models and life tables. J R Stat Soc 1972; 34: 187.

    Google Scholar 

  17. Hasle H . Myelodysplastic and myeloproliferative disorders in children. Curr Opin Pediatr 2007; 19: 1–8.

    Article  PubMed  Google Scholar 

  18. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood 2003; 102: 4290–4297.

    Article  CAS  PubMed  Google Scholar 

  19. Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999; 93: 3662–3671.

    CAS  PubMed  Google Scholar 

  20. Rocha V, Michel G, Kabbara N, Arcese W, Ortega J, Iori AP et al. Outcomes after unrelated cord blood transplantation in children with acute lymphoblastic leukemia: a Eurocord-Netcord survey (abstr# 304). Blood 2005; 106: 93a.

    Google Scholar 

  21. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 2005; 105: 1343–1347.

    Article  CAS  PubMed  Google Scholar 

  22. Locatelli F, Zecca M, Niemeyer C, Angelucci E, Arcese G, Bender-Gotze C et al. Role of allogeneic bone marrow transplantation for the treatment of myelodysplastic syndromes in childhood. The European Working Group on Childhood Myelodysplastic Syndrome (EWOG-MDS) and the Austria–Germany–Italy (AGI) Bone Marrow Transplantation Registry. Bone Marrow Transplant 1996; 18 (Suppl 2): 63–68.

    PubMed  Google Scholar 

  23. Yusuf U, Frangoul HA, Gooley TA, Woolfrey AE, Carpenter PA, Andrews RG et al. Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marrow Transplant 2004; 33: 805–814.

    Article  CAS  PubMed  Google Scholar 

  24. Davies SM, Wagner JE, Defor T, Blazar BR, Katsanis E, Kersey JH et al. Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia. Br J Haematol 1997; 96: 749–756.

    Article  CAS  PubMed  Google Scholar 

  25. Webb DK, Passmore SJ, Hann IM, Harrison G, Wheatley K, Chessells JM . Results of treatment of children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt) in Great Britain 1990–99. Br J Haematol 2002; 117: 33–39.

    Article  PubMed  Google Scholar 

  26. de Witte T, Pikkemaat F, Hermans J, van Biezen A, Mackinnan S, Cornelissen J et al. Genotypically nonidentical related donors for transplantation of patients with myelodysplastic syndromes: comparison with unrelated donor transplantation and autologous stem cell transplantation. Leukemia 2001; 15: 1878–1884.

    Article  CAS  PubMed  Google Scholar 

  27. Anderson JE, Appelbaum FR, Fisher LD, Schoch G, Shulman H, Anasetti C et al. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood 1993; 82: 677–681.

    CAS  PubMed  Google Scholar 

  28. Hasle H, Arico M, Basso G, Biondi A, Cantu Rajnoldi A, Creutzig U et al. Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS). Leukemia 1999; 13: 376–385.

    Article  CAS  PubMed  Google Scholar 

  29. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 2004; 32: 397–407.

    Article  CAS  PubMed  Google Scholar 

  30. Borojevic R, Roela RA, Rodarte RS, Thiago LS, Pasini FS, Conti FM et al. Bone marrow stroma in childhood myelodysplastic syndrome: composition, ability to sustain hematopoiesis in vitro, and altered gene expression. Leuk Res 2004; 28: 831–844.

    Article  CAS  PubMed  Google Scholar 

  31. Aizawa S, Nakano M, Iwase O, Yaguchi M, Hiramoto M, Hoshi H et al. Bone marrow stroma from refractory anemia of myelodysplastic syndrome is defective in its ability to support normal CD34-positive cell proliferation and differentiation in vitro. Leuk Res 1999; 23: 239–246.

    Article  CAS  PubMed  Google Scholar 

  32. Migliaccio AR, Adamson JW, Stevens CE, Dobrila NL, Carrier CM, Rubinstein P . Cell dose and speed of engraftment in placental/umbilical cord blood transplantation: graft progenitor cell content is a better predictor than nucleated cell quantity. Blood 2000; 96: 2717–2722.

    CAS  PubMed  Google Scholar 

  33. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.

    CAS  PubMed  Google Scholar 

  34. Parikh SH, Mendizabal A, Martin PL, Prasad VK, Szabolcs P, Driscoll TA et al. Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience. Biol Blood Marrow Transplant 2009; 15: 948–955.

    Article  PubMed  Google Scholar 

  35. Trobaugh-Lotrario AD, Kletzel M, Quinones RR, McGavran L, Proytcheva MA, Hunger SP et al. Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic stem cell transplant (HSCT). Bone Marrow Transplant 2005; 35: 143–149.

    Article  CAS  PubMed  Google Scholar 

  36. Strahm B, Locatelli F, Bader P, Ehlert K, Kremens B, Zintl F et al. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transplant 2007; 40: 329–333.

    Article  CAS  PubMed  Google Scholar 

  37. Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 2007; 110: 3064–3070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was funded by Public Health Service Grant U24-CA 756518-11 (ME, M-JZ) from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases and the National Heart Lung and Blood Institute and Inserm grant TGIR0805 (VR).

Author information

Authors and Affiliations

  1. Eurocord Office, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France

    A B M Madureira, P Teira, E Gluckman & V Rocha

  2. Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA

    M Eapen & M-J Zhang

  3. IRCCS, Ospedale Bambino Gesu′, Rome, Italy

    F Locatelli

  4. University of Pavia, Pavia, Lombardy, Italy

    F Locatelli

  5. Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    S M Davies

  6. Divisione di Onco-Ematologica e Trapianto, Università di Rome Tor Vergata, Rome, Italy

    A Picardi

  7. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    A Woolfrey

  8. Texas Transplant Institute, San Antonio, TX, USA

    K-W Chan

  9. Bone Marrow Transplantation Unit, Hôpital Saint Louis, Paris, France

    G Socié

  10. Haematology Department, Sheffield Children's Hospital, Sheffield, UK

    A Vora

  11. Hôpital Debrousse, Lyon, France

    Y Bertrand

  12. Department of Hematology, University Federal de Parana, Curitiba, Brazil

    C M Sales-Bonfim

  13. Department of Hematology and Oncology, Universitaets-Kinderklinik, Freiburg, Germany

    C Niemeyer

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  1. A B M Madureira
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on behalf of Eurocord-European Blood and Marrow Transplant Group, Center of International Blood and Marrow Transplant Registry and European Working Group on childhood MDS

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Correspondence to V Rocha.

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The authors declare no conflict of interest.

Additional information

These data were presented in part at the American Society of Hematology annual meeting, San Francisco, 2008.

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Madureira, A., Eapen, M., Locatelli, F. et al. Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation. Leukemia 25, 449–454 (2011). https://doi.org/10.1038/leu.2010.285

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